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Am J Physiol Heart Circ Physiol (January 9, 2003). doi:10.1152/ajpheart.00737.2002
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Submitted on August 29, 2002
Accepted on December 18, 2002

A Human SM22 {alpha} BAC Encompasses Regulatory Sequences for Expression in Vascular and Visceral Smooth Muscles at Fetal and Adult Stages

Rui Xu1, Ye-Shih Ho2, Raquel Ritchie3, and Li Li4*

1 Department of Internal Medicine, Wayne State University, Detroit, MI, USA
2 Environmental Health Sciences Center, Wayne State University, Detroit, MI, USA
3 Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
4 Department of Internal Medicine, Wayne State University, Detroit, MI, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Environmental Health Sciences Center, Wayne State University, Detroit, MI, USA

* To whom correspondence should be addressed. E-mail: lili{at}med.wayne.edu.

SM22{alpha} gene has widely been used to study the regulatory mechanisms of smooth muscle cell (SMC) gene expression during cardiovascular development. To determine the regulatory mechanisms for the evolutionarily conserved human SM22{alpha} (hSM22{alpha}) gene, we demonstrated that 445 bp upstream DNA sequences of hSM22{alpha} gene exhibited a high transcriptional activity in arterial SMC, not in venous nor in visceral SMCs during embryogensis. However, this promoter was gradually turned off in adulthood. Inclusion of the first intron in this promoter suppressed the promoter activity in pulmonary trunk arterial (PTA) SMCs, while the expression in other systemic vasculature remained similar to that of the hSM22-445 promoter during fetal and adult stages. To determine whether additional sequences are required for SM22{alpha} expression in all subtypes of SMCs, we examined the expression of a bacterial artificial chromosome (BAC) containing the hSM22{alpha} locus in transgenic mice. The hSM22{alpha} transgene showed similar developmental expression patterns as the endogenous mouse SM22{alpha} (mSM22{alpha}) gene, suggesting that this BAC contains essential regulatory sequences for its expression in arterial, venous and visceral tissues during development.




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